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1.  Buschke–Lowenstein tumour of glans penis☆ 
INTRODUCTION
Buschke–Löwenstein tumour, also known as Giant condyloma acuminatum, is a rare, sexually transmitted disease that affects ano-genital region. BLT is a slow growing cauliflower-like tumour, locally aggressive and destructive. Human papillomavirus has been identified as an important contributory factor in the development of tumour.
PRESENTATION OF CASE
A 45 year uncircumcised male presented with complaints of cauliflower like growth on glans penis. Growth started as a small papule on the corona sulcus at 12 O’clock position 6 months back. Patient developed pain and dysuria due to compression of urethral meatus. Patient has history of multiple sexual partners.
DISCUSSION
BLT, first described by Buschke and Lowenstein in 1925. They observed a penile lesion that clinically resembled both common condyloma acuminata and squamous cell carcinoma, but differing from both of them regarding the biological behaviour and the histopathological appearance. GCA can be differentiated from ordinary condylomas by the characteristic “pushing” rather than “infiltrating” effect that tends to compress and displace the underlying tissue.
CONCLUSION
We have successfully treated a penile BLT with surgical excision and no relapse up to 6 months. Surgical excision could be considered an effective therapy in the treatment.
doi:10.1016/j.ijscr.2014.01.023
PMCID: PMC4008846  PMID: 24705187
Giant condyloma acuminatum; Buschke–Löwenstein tumour; Surgical excision
2.  Buschke-Löwenstein's tumour presenting with urinary fistula. 
A case of Buschke-Löwenstein's tumour presenting with urinary fistula is described. The large lesion in the subpreputial sac occluded the preputial opening and infiltrated beneath the skin of the shaft of the penis resulting in a fungating growth encasing the fistulous tract. The lesion responded well to 25% podophyllin, which is reportedly unusual.
Images
PMCID: PMC1045392  PMID: 871898
3.  Intra-Abdominal Localisation of a Buschke-Lowenstein Tumour: Case Presentation and Review of the Literature 
Giant condyloma acuminatum or Buschke-Lowenstein tumour is a very rare disease which usually is located in the genital, anorectal, and perianal regions. It is regarded as a type of verrucous carcinoma occurring on anogenital mucosal surfaces where it is locally invasive but displays a benign cytology. We describe a case of a 24-year-old woman with persisting condyloma acuminata progressing to a large intra-abdominal Buschke-Lowenstein tumour. To our knowledge such an advanced stage has only been reported once before. The severity and extent of the tumour both determine the treatment and patient outcome. Treatment was impeded by cachexia, an immunosuppressive state after kidney transplantation and difficulties in establishing a reliable diagnose. Interferon treatment was started which initially led to tumour reduction but was complicated by an interferon-induced pancreatitis, pneumonia, and fasciitis necroticans resulting in death. We present a literature overview on the treatment options for a Buschke-Lowenstein tumour, with emphasis on interferon therapy, with all the advantages and disadvantages.
doi:10.1155/2013/187682
PMCID: PMC3789409  PMID: 24159412
4.  Rapid progression of an anal Buschke–Löwenstein tumour into a metastasising squamous cell carcinoma in an HIV-infected patient 
Sexually transmitted infections  2009;85(4):261-263.
Background
Buschke–Löwenstein tumour (BLT) of the anogenitalia is a locally invasive, destructively growing verrucous carcinoma that does not metastasise. Histologically BLT resembles benign condylomata acuminata. Nevertheless, the tumour grows relentlessly and may rarely progress into squamous cell cancer (SCC).
Results
A human immunodeficiency virus (HIV)-infected immunosuppressed patient developed (peri)anal warts accompanied by recurrent abscesses and fistulae. Histology revealed condylomata acuminata, and low-risk genital human papillomavirus (HPV) type 11b was detected. Six months later, the tumour had progressed into an ulcerated SCC that destroyed the rectum and perineum, with metastases to the inguinal lymph nodes. Whereas highly active antiretroviral therapy (HAART) effectively suppressed HIV replication, radiochemotherapy plus anti-EGFR antibody did not halt tumour progression, and the patient died from tumour-cachexia.
Discussion
As far as is known, this is the first report demonstrating rapid progression of a BLT into a metastasising SCC in an HIV-infected patient.
doi:10.1136/sti.2008.034959
PMCID: PMC3935459  PMID: 19625295
5.  Perianal giant condyloma acuminata [buschke lowenstein tumour] — first case report from the Kashmir valley 
The Indian Journal of Surgery  2008;69(5):203-205.
Buschke Lowenstein tumour or giant condyloma acuminata is a rare entity with only less then 50 cases reported in English literature so far. No such case has been reported from the Kashmir valley. They are considered as intermediate lesions between simple condyloma acuminata and invasive squamous cell carcinoma. A 57-year-old heterosexual male presented with a giant perianal condyloma. The lesion was surgically excised completely. Postoperatively patient was put on topical 5-FU ointment. Patient is recurrence free 6 months after surgery. The giant condyloma acuminate is an aggressive tumour with propensity for recurrance and malignant transformation. Surgical excision is the treatment of choice. One such rare case is discussed with review of literature.
doi:10.1007/s12262-007-0023-3
PMCID: PMC3452581  PMID: 23132984
Condyloma acuminate; Buschke lowenstein; Perianal
6.  A surgical approach to giant condyloma (Buschke-Löwenstein tumour) with underlying superficial vulvar carcinoma: A case report 
Oncology Letters  2012;5(2):541-543.
Anogenital warts (condyloma acuminatum or venereal warts) are a common sexually transmitted disease in males and females. Common clinical treatment of anogenital warts is conservative, however, in extreme cases conservative therapy is insufficient and surgical excision is required. Giant condyloma acuminata (Buschke-Löwenstein tumour) is an extremely rare clinical type of genital wart, characterised by aggressive down growth into underlying dermal structures. A 55-year-old female presented with cauliflower-like growth over the anogenital and sacral region, earlier diagnosed as condyloma acuminatum which was resistant to conservative therapy. During the period between 2005 and 2008 the patient underwent five surgical procedures. Due to the size and location of the tumour, gynaecological and plastic surgeons were involved in the procedures. In addition, definitive histology examination identified a superficial vulvar carcinoma.
doi:10.3892/ol.2012.1027
PMCID: PMC3573067  PMID: 23420321
giant condyloma; Buschke-Löwenstein tumour; vulvar carcinoma; surgery
7.  Successful Treatment of Buschke–Löwenstein Tumour by Surgical Excision Alone 
A 48-year-old man presented with multiple warts in groin for 1 year, which progressively increased in size. Local examination showed large vegetative growth in perianal area. Full thickness excision of involved skin and lesions was undertaken by electrocautery. Entire wound was left open to heal by secondary intention. Histopathological examination suggested Buschke-Löwenstein tumour. Postoperative follow-up for more than 2 years showed the absence of any recurrence.
doi:10.4103/0974-2077.74496
PMCID: PMC3047737  PMID: 21430832
Buschke-Löwenstein tumour; giant condyloma acuminatum; wide radical excision
8.  Selectionist and Evolutionary Approaches to Brain Function: A Critical Appraisal 
We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman’s theory of neuronal group selection, Changeux’s theory of synaptic selection and selective stabilization of pre-representations, Seung’s Darwinian synapse, Loewenstein’s synaptic melioration, Adam’s selfish synapse, and Calvin’s replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price’s covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise.
doi:10.3389/fncom.2012.00024
PMCID: PMC3337445  PMID: 22557963
neural Darwinism; neuronal group selection; neuronal replicator hypothesis; Darwinian neurodynamics; Izhikevich spiking networks; causal inference; price equation; hill-climbers
9.  The impact of Improving Outcomes Guidance on the management and outcomes of patients with carcinoma of the penis 
INTRODUCTION
The Improving Outcomes Guidance (IOG) for patients with carcinoma of the penis states that treatment should be provided supraregionally to populations of 4 million or greater who treat over 25 cases of penis cancer each year. This study assesses the impact of this guidance on the management and outcomes of patients with the disease in our region.
PATIENTS AND METHODS
We retrospectively compared the records of 44 patients with carcinoma of the penis treated in our institution between 1969 and 1990 with 101 patients treated between 2002 and 2006, i.e. after supraregional centralisation of the service.
RESULTS
There was no significant change in the stage or grade of the tumours. However, the results show that, in modern times, there was a significant increase in the amount of penis-preserving and nodal surgery as well as a fall in mortality. The improved survival is greatest in patients with poorly-differentiated disease who may, therefore, have benefited from aggressive nodal surgery.
CONCLUSIONS
The centralisation of surgery for carcinoma of the penis results in improved outcomes both in terms of preservation and improved survival and this supports the IOG guidance.
doi:10.1308/003588410X12518836439047
PMCID: PMC3024616  PMID: 20056060
Improving Outcomes Guidance; Penis cancer; Penis preservation; Survival
10.  A rare case of carcinoma cuniculatum of the penis in a 55-year-old 
Carcinoma cuniculatum of the penis is an extremely rare variant of squamous cell carcinoma characterized by an endophytic deeply branching and burrowing growth pattern. One documented case series demonstrated afflicted patients ranging in age from 73–83 years with the tumour located on the glans penis, coronal sulcus or foreskin. We report a case of a 55-year-old with disease located on the ventral aspect of the shaft of the penis. The tumour was invasive into the deep dermal connective tissue, comparatively superficial to all previous documented cases. He subsequently underwent a partial penectomy. The case is discussed with a brief review of the literature.
PMCID: PMC2950764  PMID: 20944791
11.  Secondary penile tumours revisited 
Objective
To highlight the salient features of metastatic malignancies involving the penis, with special reference to the primary tumour sites, metastatic mechanisms, clinical features, differential diagnosis, treatment and prognosis.
Methods
A comprehensive search of the literature was performed using MEDLINE and EMBASE, using the keywords 'penis', 'secondary malignancy', 'metastasis' and 'malignant priapism' to identify reviews and case reports of secondary penile malignancy. A case of rare clinical presentation of metastatic penile lesion is presented along with the review of the literature.
Conclusion
Secondary malignancy of the penis is a rare clinical entity, despite the rich vascularisation of this organ. The majority of metastatic lesions take their origin from the neighbouring genito-urinary organs, mainly prostate and bladder. These lesions are often associated with disseminated malignancy and hence have a poor outcome. Nodular or ulcerative lesions involving the corpora cavernosa or priapism are the main modes of clinical presentation. In most cases, only palliative or supportive therapy is indicated.
doi:10.1186/1477-7800-3-33
PMCID: PMC1618838  PMID: 17032461
12.  Primary penile malignant lymphoma: report of a rare case 
A 73-year-old male presented with a 3-month history of two penile masses: one on the shaft and one on the glans penis. Both lesions were poorly defined, fixated and without tenderness. The sizes were 1.0 × 1.0 × 1.0 cm and 1.2 × 1.5 × 1.5 cm, respectively. The patient underwent lumpectomy of the glans penis; we confirmed malignant lymphoma of the glans penis (B-cell derived; diffused large B-cell) by postoperative pathological examinations. CHOP (cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone) chemotherapy was administered. The patient was tumour-free at the 33-month follow-up.
doi:10.5489/cuaj.11299
PMCID: PMC3529737  PMID: 23283104
13.  A Review of Penile Cancer 
Advances in Urology  2010;2009:415062.
Cancer of the penis is a rare tumour in Europe and mainly affects the elderly patient population. The aim of this paper was to analyse and study the characteristics of this tumour, in our patient population. Materials and Methods. A retrospective study was conducted on penile tumours diagnosed and treated in the Urology Department of the Hospital Universitario La Paz, Madrid, in the last ten years. Results. A total of 34 patients were diagnosed and treated. The mean age at presentation was 71.27 years. The mean time between symptoms and the first consultation was 12.54 months with a median of 6 months. The most common form of presentation was balanoposthitis (32%) and the most common site in our series was the glans. Partial penectomy was performed in 22 cases, total amputation in 8, and local excision in 3. Discussion. Carcinoma of the penis is a pathology which mostly affects elderly patients; in our series, the highest incidence was observed in patients in the group aged 75–84 years. The most common histological type was epidermoid carcinoma in its various forms of presentation. We recorded a mortality of 23%. Conclusion. Penile carcinoma is a rare pathology which affects elderly persons and is diagnosed late.
doi:10.1155/2009/415062
PMCID: PMC2825548  PMID: 20182534
14.  Giant fibroepithelial polyp of the glans penis not associated with condom-catheter use: A case report and literature review 
Canadian Urological Association Journal  2013;7(9-10):E621-E624.
Fibroepithelial polyps are rare benign tumours of the glans penis; there are only a few reported cases. The pathogenesis is unknown. However, they have been linked with chronic condom catheter use or prior penile surgery. We report a case of a 62-year-old man with a large fibroepithelial polyp of the glans penis of 11 years duration, which was not associated with condom catheter use or prior surgery. The mass was large, measuring 7 × 5 × 3 cm. Fibroepithelial polyps have been reported in a range of genito-urinary sites in males and females, adults and children, and in rare cases may be associated with malignant transformation. They should be considered in the differential diagnosis of both cutaneous and mucosal genitourinary lesions.
doi:10.5489/cuaj.506
PMCID: PMC3776044  PMID: 24069111
15.  Primary Leiomyosarcoma of the Penis: A Case Report 
Primary leiomyosarcoma of the penis is a very rare tumour. Only 46 cases have been reported in the English medical literature. We are presenting this case of a 59-year-old patient with a ulceroproliferative growth in his penis. Histopathology was a high grade spindle cell sarcoma, which was proved by immunohistochemistry to be a leiomyosarcoma.
doi:10.7860/JCDR/2014/6723.3808
PMCID: PMC3939536  PMID: 24596756
Spindle cell sarcoma; Immunohistochemistry; Leiomyosarcoma
16.  Memory disorders in probable Alzheimer's disease: the role of hippocampal atrophy as shown with MRI. 
Magnetic resonance based volumetric measures of hippocampal formation, amygdala (A), caudate nucleus (CN), normalised for total intracranial volume (TIV), were analysed in relation to measures of cognitive deterioration and specific features of memory functions in 18 patients with probable Alzheimer's disease. Neuropsychological examination included the mini mental state examination (MMSE), the Mattis dementia rating scale (DRS), tests of executive functions, assessment of language abilities and praxis, the Wechsler memory scale (WMS), the California verbal learning test (CVLT) and the Grober and Buschke test. The volume of the hippocampal formation (HF/TIV) was correlated with specific memory variables: memory quotient and paired associates of the WMS; intrusions and discriminability at recognition for the Grober and Buschke test. By contrast, except for intrusions, no correlations were found between memory variables and the volume of amygdala (A/TIV). No correlations were found between the volume of caudate nuclei (CN/TIV) and any neuropsychological score. The volume of the hippocampal formation was therefore selectively related to quantitative and qualitative aspects of memory performance in patients with probable Alzheimer's disease.
Images
PMCID: PMC1073492  PMID: 7745409
17.  Buschke-Lowenstein tumor 
Background
Verrucous carcinoma of the skin and mucosa is an uncommon type of well-differentiated squamous cell carcinoma. When it is present in the genitoanal region the term used is Buschke-Lowenstein tumor. The human papillomavirus seems to be implicated in its aetiology. Treatment is controversial. Topical chemotherapy, radiotherapy, immunotherapy and radical surgery have been employed.
Main observations
We report a rapidly progressing penile verrucous carcinoma which was treated sucessfuly with conservative surgery and CO2 laser.
Conclusion
Treatment with CO2 laser in combination with conservative surgery may be a therapeutic option in Buschke-Lowenstein tumor.
doi:10.3315/jdcr.2008.1019
PMCID: PMC3157782  PMID: 21886716
condylomata acuminata; lasers; penile neoplasms; squamous cell carcinoma; verrucous carcinoma
18.  Successful treatment of paraneoplastic hypercalcemia in a patient with giant condyloma acuminatum: a case report 
Introduction
While paraneoplastic syndromes in patients with malignant and metastasizing tumors are common, they are rarely associated with skin tumors showing predominantly local growth patterns. This case report relates to a patient with giant condyloma acuminatum, also called Buschke-Löwenstein tumor, with paraneoplastic hypercalcemia, who was successfully treated with conservative treatment.
Case presentation
The patient in question is a 48-year-old German man with a giant periscrotal tumor. Before and during the therapy, two episodes of symptomatic hypercalcemia occurred, which were successfully treated by bisphosphonates, intravenous fluids and diuretics. No evidence of lytic bone affection was found.
Conclusions
Paraneoplastic hypercalcemia may occur in patients who have a Buschke-Löwenstein tumor. For patients, where surgery is not an option, established medical therapies like bisphosphonates may be useful in addition to diuretics and infusions.
doi:10.1186/1752-1947-7-251
PMCID: PMC3843559  PMID: 24200238
Paraneoplastic hypercalcemia; Buschke-Löwenstein tumor; Giant condyloma acuminatum
19.  Reconstructive surgery in anal giant condyloma: Report of two cases☆ 
INTRODUCTION
Giant anal condyloma also called Buschke–Löwenstein tumor is a rare sexually transmitted disease involving anogenital region with potential malignant degeneration into invasive squamous carcinoma. Complete surgical excision is the treatment of choice and often wide wounds are necessary to reach clear margins and prevent recurrence.
PRESENTATION OF CASE
The authors present two cases treated with an S-plasty rotating and a bilateral house advancement flap respectively with good functional result.
DISCUSSION
Giant anal condyloma also called Buschke–Löwenstein tumor is a large exophytic, cauliflower-like mass that is characterized by local aggressive behavior. Immunosuppression favors rapid growth of the condylomas and increases the risk of their malignant transformation. In limited lesions primary excision can be safely performed leaving wounds open to granulate while in more extensive lesions flap or skin graft coverage is preferable to decrease the length of recovery and minimize risk of severe anal stricture. Abdominoperineal resection should be performed for more extensive lesions with deep invasion, malignant transformation or tumor recurrence.
CONCLUSION
Giant anal condyloma also called Buschke–Löwenstein is a rare pathology with mainly sporadic single center experience reported in literature. Surgical complete excision remains the best treatment although elevate should be eventual recurrence. No sufficient data are available to recommend any medical treatment such as interferon, radiotherapy or chemotherapy.
doi:10.1016/j.ijscr.2013.08.020
PMCID: PMC3860016  PMID: 24240074
Giant condyloma; Buschke–Löwenstein tumor; S-plasty rotating flap; House advancement flap
20.  Verrucous carcinoma arising in an extended giant condyloma acuminatum (Buschke–Löwenstein tumor): a case report and review of the literature 
Introduction
Verrucous carcinoma of the external genitalia and perianal region is a rare variant of well-differentiated squamous cell carcinoma. It has been reported to have limited metastatic potential.
Case presentation
We report the case of a 54 year-old Moroccan man who presented with locally advanced giant condyloma acuminatum (Buschke–Löwenstein tumor) after prolonged intervals of neglect (approximately 10 years). The disease covered his suprapubic, external genitalia and perianal region. It was locally aggressive with extensive tissue destruction. After a biopsy of the lesion, the diagnosis of verrucous carcinoma was confirmed. He initially received chemoradiotherapy, followed by extensive local excision, but he developed septic shock and died a few days later.
Conclusions
The purpose of this case report is to present a case of verrucous carcinoma arising in an extensive giant condyloma acuminatum (Buschke–Löwenstein tumor) and discuss the literature on its diagnosis and management.
doi:10.1186/1752-1947-7-273
PMCID: PMC3895673  PMID: 24354693
Buschke–Löwenstein tumor; Chemoradiotherapy; Condyloma acuminatum; Human papillomavirus; Verrucous carcinoma
21.  Giant Anorectal Condyloma Acuminatum of Buschke–Lowenstein: Successful Plastic Reconstruction with Bilateral Gluteal Musculocutaneous V-Y Advancement Flap 
The Indian Journal of Surgery  2012;75(Suppl 1):168-170.
A 58-year-old male patient presented with an anorectal verrucous carcinoma, also known as Buschke–Lowenstein tumor. Clinically, the lesion of the patient best resembled giant condyloma acuminatum with a cauliflower-like appearance. The diagnosis was confirmed with biopsy and an abdominoperineal resection was performed. The perineal defect was reconstructed with bilateral gluteal musculocutaneous V-Y advancement flap. Both functional and cosmetic results 6 years after the operation were excellent. To date, no recurrence has been noted. As long as one is aware of its existence and of its characteristic appearances, the Buschke–Lowenstein tumor is fairly easily diagnosed. The treatment of choice remains surgical resection, and adequate follow-up is essential.
doi:10.1007/s12262-012-0579-4
PMCID: PMC3693380  PMID: 24426553
Verrucous carcinoma; Buschke–Lowenstein tumor; Giant condyloma acuminatum; Abdominoperineal resection; V-Y advancement flap
22.  Effects of craving and DRD4 VNTR genotype on the relative value of alcohol: an initial human laboratory study 
Background
Craving for alcohol is a highly controversial subjective construct and may be clarified by Loewenstein's visceral theory, which emphasizes craving's behavioral effects on the relative value of alcohol. Based on the visceral theory, this study examined the effects of a craving induction on the relative value of alcohol as measured by a behavioral choice task. In addition, based on previous evidence of its role in the expression of craving, the influence of DRD4 VNTR genotype (DRD4-L vs. DRD4-S) was also examined.
Methods
Thirty-five heavy drinkers (54% male; 31% DRD4-L) were randomly assigned to receive either a craving induction (exposure to personally relevant alcohol cues) or a control induction (exposure to neutral cues), which was followed by an alcohol-money choice task. Participants were assessed for craving and positive/negative affect throughout the procedure, and relative value of alcohol was derived from participant choices for alcohol versus money. DRD4 VNTR status was assessed retrospectively via buccal samples using previously established protocols.
Results
Factorial analysis of the craving induction revealed that it was associated with significant increase in craving (p < .001), but not greater relative value of alcohol. Factorial analyses including DRD4 VNTR genotype of did not suggest an influence on reactivity to the craving induction, although this analysis was substantially compromised by small cell sample sizes. Continuous analyses revealed that craving was significantly associated with the relative value of alcohol (p < .05) and possession of the DRD4-L allele further amplified this relationship (p < .001).
Conclusion
These results are interpreted as generally supporting Loewenstein's visceral theory of craving and evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol. Methodological limitations, mechanisms underlying these findings, and future directions are discussed.
doi:10.1186/1744-9081-3-11
PMCID: PMC1805446  PMID: 17309802
23.  In vitro interaction of the human immunodeficiency virus type 1 Tat transactivator and the general transcription factor TFIIB with the cellular protein TAP. 
Journal of Virology  1995;69(5):3017-3023.
We have reported the molecular cloning, expression, and characterization of a human cellular protein, TAP, which possesses a strong transcriptional activation domain and binds the human immunodeficiency virus type 1 Tat transactivator in vitro and in vivo (L. Yu, Z. Zhang, P.M. Loewenstein, K. Desai, Q. Tang, D. Mao, J.S. Symington, and M. Green, J. Virol. 69:3007-3016, 1995). Here we show that TAP binds the general transcription factor TFIIB. Furthermore, we delineate the binding domains of TAP, Tat, and TFIIB, as well as measure the strengths and specificity of these protein-protein interactions. TAP binds strongly to Tat, with a Kd of (approximately 2 to 5) x 10(-7) M. The Tat activation region contains a 17-amino-acid conserved core domain which is the single contact site for TAP. Single-amino-acid substitutions within the Tat core domain inactivate transactivation in vivo and in vitro and greatly reduce binding of Tat to TAP in vitro. TAP binds strongly to TFIIB, with about the same Kd as for Tat. The interaction between TAP and TFIIB requires a sequence near the carboxy terminus of TFIIB which is also required for binding the strong acidic activator VP16. The contact sites for Tat and TFIIB map within the TAP C-terminal region, which contains the TAP activation domain. These combined results are consistent with the hypothesis that TAP is a cellular coactivator that bridges the Tat transactivator to the general transcription machinery via TFIIB.
PMCID: PMC189001  PMID: 7707528
24.  Differential regulation of communication by retinoic acid in homologous and heterologous junctions between normal and transformed cells 
The Journal of Cell Biology  1991;113(2):371-379.
The permeability of junctions between cells of the same type (homologous junctions) is greatly increased by retinoic acid (10(-9)- 10(-8) M), a probable morphogen, and this responsiveness is shared by a variety of normal and transformed cell types (Mehta, P.P., J.S. Bertram, and W.R. Loewenstein. 1989. J. Cell Biol. 108:1053-1065). Here we report that the heterologous junctions between the normal and transformed cells respond in the opposite direction; their permeability is reduced by retinoic acid (greater than or equal to 10(-9) M) and its benzoic acid derivative tetrahydrotetramethylnaphthalenylpropenylbenzoic acid (greater than or equal to 10(-11) M). The opposite responses of the two classes of junction are shown to be concurrent; in cocultures of normal 10T1/2 cells and their methylcholanthrene-transformed counterparts, the permeability of the heterologous junctions, which is lower than that of the homologous junctions to start with, falls (within 20 h of retinoid application), at the same time that the permeability of the homologous junctions rises in both cell types. Such a counter-regulation requires a minimum of three degrees of cellular differentiation. A model is proposed in which the differentiations reside in a trio of junctional channel protein. The principle of the model may have wide applications in the regulation of intercellular communication at tissue boundaries, including embryonic ones.
PMCID: PMC2288939  PMID: 2010467
25.  What is for me is not for you: brain correlates of intertemporal choice for self and other 
People have present-biased preferences: they choose more impatiently when choosing between an immediate reward and a delayed reward, than when choosing between a delayed reward and a more delayed reward. Following McClure et al. [McClure, S.M., Laibson, D.I., Loewenstein, G., Cohen, J.D. (2004). Separate neural systems value immediate and delayed monetary rewards. Science, 306, 503.], we find that areas in the dopaminergic reward system show greater activation when a binary choice set includes both an immediate reward and a delayed reward in contrast to activation measured when the binary choice set contains only delayed rewards. The presence of an immediate reward in the choice set elevates activation of the ventral striatum, pregenual anterior cingulate cortex and anterior medial prefrontal cortex. These dopaminergic reward areas are also responsive to the identity of the recipient of the reward. Even an immediate reward does not activate these dopaminergic regions when the decision is being made for another person. Our results support the hypotheses that participants show less affective engagement (i) when they are making choices for themselves that only involve options in the future or (ii) when they are making choices for someone else. As hypothesized, we also find that behavioral choices reflect more patience when choosing for someone else.
doi:10.1093/scan/nsq046
PMCID: PMC3073390  PMID: 20529885
present-biased preferences; intertemporal discounting; fMRI; multiple systems hypothesis

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